Menaquinone or vitamin K2 is involved in the carboxylation of certain glutamate residues in proteins to form gamma-carboxyglutamate residues (abbreviated Gla-residues). The modified residues are often (but not always) situated within specific protein domains called Gla domains. Gla-residues are usually involved in binding calcium. The Gla-residues are essential for the biological activity of all known Gla-proteins (Furie B, Bouchard B A, Furie B C; Blood 93 (6): 1798-808). To date, 14 human proteins with Gla domains have been discovered, and they play key roles in the regulation of three physiological processes, such as blood coagulation (prothrombin (factor II), factors VII, IX, X, protein C, protein S and protein Z); bone metabolism (osteocalcin, also called bone Gla-protein (BGP), and matrix gla protein (MGP); and vascular biology.
Accordingly, menaquinone deficiency may induce several pathologies such as for example bleeding, coagulation dysfunctions, osteoporosis . . . . Typically, the groups of patients which are considered to be particularly exposed to a menaquinone deficiency are the new born, the elderly, the patients having liver, bile or intestinal dysfunctions, and patients having chronic antibiotic treatment.
Several methods have been proposed in the prior art to supplement the menaquinone deficiency of these patients. One of these methods consists to administer to these patients menaquinone-producing bacteria. Indeed, menaquinone is produced by the bacteria of the intestinal flora, and in particular by the bacteria of the species Escherichia coli, Bacillus subtilis and Bacteroides subsp. Menaquinone is also produced by several lactic acid bacteria, such as for example the bacteria of the genera Bifidobacterium, Lactococcus, Leuconostoc, Enteroccocus and Propionibacterium. In particular, a specific variant of Lactococcus lactis subsp. cremoris having the ability to produce more menaquinone than the corresponding wild type strain has been recently disclosed in WO 2008/040793.
However, having strains capable of producing higher amounts of menaquinone would be very interesting.